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ABSTRACT Interleukin (Il)-12 is a heterodimeric cytokine composed of 35 and 40 kD chains that plays a key role in the induction of Th1 cells, a T cell subset involved in many autoimmune

diseases. We report here the cDNA sequence encoding the IL-12 p40 subunit from the autoimmune-prone non-obese diabetic (NOD) mouse, which spontaneously develops type 1 diabetes. Compared

with the C57BL/6 sequence, there are two base changes that lead to amino acid replacements. Other autoimmune-prone strains, but not the diabetes-resistant NOR strain, share the same allele

as NOD. We found both trans- and cis- allele-dependent effects on levels of basal and induced IL-12p40 expression. Furthermore, we show that one of these changes results in a structural

change in the p40 molecule, as evidenced by the failure of a monoclonal antibody to bind NOD IL-12. These findings have implications for the predisposition to autoimmune responses in NOD and

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J_ 1998 15: 115–130 Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * The Walter and Eliza Hall Institute of Medical Research, PO Royal

Melbourne Hospital, Victoria, 3050, Australia S I Ymer, D Huang, K Branson & G Morahan * Roche Milano Ricerche, Via Olgettina 58, Milano, 20132, Italy G Penna, S Gregori & L Adorini

Authors * S I Ymer View author publications You can also search for this author inPubMed Google Scholar * D Huang View author publications You can also search for this author inPubMed Google

Scholar * G Penna View author publications You can also search for this author inPubMed Google Scholar * S Gregori View author publications You can also search for this author inPubMed 

Google Scholar * K Branson View author publications You can also search for this author inPubMed Google Scholar * L Adorini View author publications You can also search for this author

inPubMed Google Scholar * G Morahan View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to G Morahan. ADDITIONAL

INFORMATION This work was supported by the National Health and Medical Research Council of Australia, by a special Diabetes Interdisciplinary Research Program grant from the NHMRC-Juvenile

Diabetes Foundation International and by the CRC for Discovery of Genes for Common Human Diseases. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ymer,

S., Huang, D., Penna, G. _et al._ Polymorphisms in the Il12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains. _Genes Immun_ 3, 151–157 (2002).

https://doi.org/10.1038/sj.gene.6363849 Download citation * Received: 20 November 2001 * Accepted: 02 December 2001 * Published: 21 May 2002 * Issue Date: 01 May 2002 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * IL12b * autoimmunity * immunogenetics * genetic

regulation * epitope